PXD009283-1

PXD009283 is an original dataset announced via ProteomeXchange.

Title	The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease
Description	The marsupial Tasmanian devil (Sarcophilus harrisii) faces extinction due to transmissible devil facial tumor disease (DFTD). To unveil the culprit molecular underpinnings, we designed an approach that combines sensitivity to drugs with an integrated systems-biology characterization. Sensitivity to inhibitors of the ERBB family of receptor tyrosine kinases correlated with their overexpression, suggesting a causative link. Proteomic and DNA methylation analyses revealed tumor-specific signatures linked to oncogenic signaling hubs including evolutionary conserved STAT3. Indeed, inhibition of ERBB blocked phosphorylation of STAT3 and arrested cancer cells. Blockade of ERBB signaling prevented tumor growth in a xenograft model and resulted in recovery of MHC-I gene expression. This link between the hyperactive ERBB-STAT3 axis and decreased MHC-I mediated tumor immunosurveillance provides mechanistic insights into horizontal transmissibility and lets us propose a dual chemo-immunotherapeutic strategy to save Tasmanian devils from DFTD.
HostingRepository	PRIDE
AnnounceDate	2019-01-18
AnnouncementXML	Submission_2019-01-18_03:24:04.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alexandra Popa
SpeciesList	scientific name: Sarcophilus harrisii; NCBI TaxID: 9305;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2018-03-21 07:05:41	ID requested
⏵ 1	2019-01-18 03:24:05	announced

Kosack L, Wingelhofer B, Popa A, Orlova A, Agerer B, Vilagos B, Majek P, Parapatics K, Lercher A, Ringler A, Klughammer J, Smyth M, Khamina K, Baazim H, de Araujo ED, Rosa DA, Park J, Tin G, Ahmar S, Gunning PT, Bock C, Siddle HV, Woods GM, Kubicek S, Murchison EP, Bennett KL, Moriggl R, Bergthaler A, The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease. Cancer Cell, 35(1):125-139.e9(2019) [pubmed]

curator keyword: Biological

submitter keyword: Tasmanian devil, DFTD, transmissible cancer, ERBB

Dr Andreas Bergthaler
contact affiliation	CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences Lazarettgasse 14, AKH BT 25.3 1090 Vienna, Austria
contact email	abergthaler@cemm.oeaw.ac.at
lab head
Alexandra Popa
contact affiliation	CeMM
contact email	apopa@cemm.oeaw.ac.at
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/01/PXD009283

PRIDE project URI

• PRIDE
  1. PXD009283
     1. Label: PRIDE project
     2. Name: The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease